M&R Session 7- Receptor-effector Signalling Via G Proteins. Flashcards
What is signal transduction?
When extracellular ligand binding to a receptor requires transducing via intracellular proteins into an intracellular response.
Which cellular functions require G-protein coupled receptors? (5)
- muscle contraction
- stimulus-secretion coupling
- catabolic and anabolic metabolic processes
- taste and smell
- light perception.
What are the 3 super families of cell surface receptor?
- ligand gated ion channels
- receptors with intrinsic enzymatic activity
- G protein coupled (7TMD) receptors
What is the result of genetic changes/mutations to GPCRs?
-loss or gain of function
Describe the 4 basic features of GPCRs
- 7TMDs
- extracellular N terminal
- intracellular C terminal
- single polypeptide chain
Where are the 2 possible binding sites of GPCRs?
- within 2-3 of the transmembrane spanning domains.
- extracellularly at the an terminal or some other domain
Briefly outline how G proteins work
- agonist binds and causes activation of GPCR
- interaction between GPCR and G protein causes GDP-> GTP on alpha subunit of G protein.
- as a result, the alpha subunit and the beta-gamma subunit lose affinity and dissociate.
- each subunit has an effect on an effector.
How is G protein activity terminated?
The hydrolysis of GTP back to GDP on the alpha subunit. This allows the recombination of the alpha and beta-gamma subunits.
What are the structural and functional names of G proteins?
Structural- heterotrimeric
Functional- dimeric
Why can G proteins be thought of as on/off switches and timers?
On because of receptor facilitated exchange of GDP for GTP.
Timer because the off switch is governed by the length of time it takes for GTP hydrolysis back to GDP on the alpha subunit.
What is a G protein also know as?
Guanine nucleotide binding protein
What is the effect of the cholera toxin?
It eliminates the GTPase activity of the Gs subunit and therefore causes it to be irreversibly activated.
What is the consequence of the pertussis toxin?
It binds to the GPCR and interferes with GDP/GTP exchange on Gi subunit, meaning that it is irreversibly inactivated.
